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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Heterogeneous gene expression from the inactive X chromosome: an X-linked gene that escapes X inactivation in some human cell lines but is inactivated in others.

In mammalian females, most genes on one X chromosome are transcriptionally silenced as a result of X chromosome inactivation. Whereas it is well established that some X-linked genes "escape" X inactivation and are expressed from both active (Xa) and inactive (Xi) X chromosomes, most models for the chromosomal control of X-linked gene expression assume that the X inactivation status of a given gene is constant among different females within a population. In this report, we test the expression of human X-linked genes in primary cell lines from females with complete nonrandom X inactivation, by using transcribed polymorphisms to distinguish Xa and Xi expression. Six X-linked genes used to document this assay system showed monoallelic expression in all informative cell lines, consistent with X inactivation. However, a novel pattern of expression was observed for another gene, REP1; monoallelic expression, indicating inactivation, was detected in some lines, whereas biallelic expression, indicating escape from inactivation, was detected in others. Furthermore, levels of Xi expression varied among cell lines that expressed REP1. The cellular basis of Xi expression was examined by expression assays in single cells. These data indicate that REP1 is expressed from the Xi in all cells, but that the level of expression relative to Xa levels is reduced. These findings suggest that Xi gene expression is under a previously unsuspected level of genetic or epigenetic control, likely involving local or regional changes in chromatin organization that determine whether a gene escapes or is subject to X inactivation.[1]

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